Trial Outcomes & Findings for Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies (NCT NCT03317496)

Last Updated: 2023-08-29

Results Overview

DLTs=occurrence of any AEs attributable to study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting \>7days;febrile neutropenia with body temperature \>=38 degree Celsius for \>1hour; G\>=3 neutropenic infection(absolute neutrophil count \<1.0\*10\^9/L),G\>=3 thrombocytopenia (platelet count\<50.0-25.0\*10\^9/L)with bleeding;G4 thrombocytopenia(PC\<25.0\*10\^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for \>3days despite medical treatment(nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST \>3\*upper limit of normal(ULN)if normal at baseline or 2\*Baseline(\>ULN at baseline)with total bilirubin \>2\*ULN and alkaline phosphatase \<2\*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of \>=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. DLT-evaluable analysis set.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)

Results posted on

2023-08-29

Participant Flow

The study was conducted in 2 phases: Phase 1b (lead-in phase) and Phase 2 (cohort expansion phase). Phase 2 was conducted at the highest dose level of avelumab which was determined safe for participants in Phase 1b.

Phase 1b lead-in:49 participants signed inform consent form(ICF).18 participants did not meet eligibility criteria and not enrolled,31 participants enrolled and assigned to treatment. Phase 2:52 participants signed ICF.16 participants did not meet eligibility criteria and not enrolled,36 participants enrolled,1 was not assigned to treatment and 35 assigned to treatment.

Participant milestones

Participant milestones
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Phase 1b Lead-in: Treatment STARTED	6	13	6	6	0
Phase 1b Lead-in: Treatment COMPLETED	0	0	0	0	0
Phase 1b Lead-in: Treatment NOT COMPLETED	6	13	6	6	0
Phase 1b Lead-in: Follow-up STARTED	6	12	5	6	0
Phase 1b Lead-in: Follow-up COMPLETED	0	0	0	0	0
Phase 1b Lead-in: Follow-up NOT COMPLETED	6	12	5	6	0
Phase 2: Treatment STARTED	0	0	0	0	35
Phase 2: Treatment COMPLETED	0	0	0	0	0
Phase 2: Treatment NOT COMPLETED	0	0	0	0	35
Phase 2: Follow-up STARTED	0	0	0	0	33
Phase 2: Follow-up COMPLETED	0	0	0	0	0
Phase 2: Follow-up NOT COMPLETED	0	0	0	0	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.
Phase 1b Lead-in: Treatment Adverse Event	3	4	1	1	0
Phase 1b Lead-in: Treatment Physician Decision	0	1	0	0	0
Phase 1b Lead-in: Treatment Death	0	0	1	0	0
Phase 1b Lead-in: Treatment Progressive Disease	1	6	3	4	0
Phase 1b Lead-in: Treatment Other	2	1	0	0	0
Phase 1b Lead-in: Treatment Global deterioration of health status	0	0	1	0	0
Phase 1b Lead-in: Treatment Study terminated by sponsor	0	1	0	1	0
Phase 1b Lead-in: Follow-up Death	3	8	4	4	0
Phase 1b Lead-in: Follow-up Lost to Follow-up	1	0	0	0	0
Phase 1b Lead-in: Follow-up Withdrawal by Subject	0	0	1	0	0
Phase 1b Lead-in: Follow-up Other	0	1	0	1	0
Phase 1b Lead-in: Follow-up Study terminated by sponsor	2	3	0	1	0
Phase 2: Treatment Adverse Event	0	0	0	0	6
Phase 2: Treatment Progressive disease	0	0	0	0	22
Phase 2: Treatment Other	0	0	0	0	4
Phase 2: Treatment Withdrawal by Subject	0	0	0	0	1
Phase 2: Treatment Physician Decision	0	0	0	0	1
Phase 2: Treatment Death	0	0	0	0	1
Phase 2: Follow-up Death	0	0	0	0	24
Phase 2: Follow-up Lost to Follow-up	0	0	0	0	1
Phase 2: Follow-up Other	0	0	0	0	1
Phase 2: Follow-up Study terminated by sponsor	0	0	0	0	7

Baseline Characteristics

Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.	Total n=66 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants	25 Participants n=21 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	27 Participants n=4 Participants	41 Participants n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants	17 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	31 Participants n=4 Participants	49 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	37 Participants n=4 Participants	60 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	11 Participants n=7 Participants	5 Participants n=5 Participants	37 Participants n=4 Participants	59 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)

Population: The DLT analysis set is a subset of the safety analysis set and includes all enrolled participants in the Phase 1b lead-in who are eligible for the study, receive at least one dose of the combination treatment, and either experience DLT during the first 2 cycles (6 weeks) of treatment, or complete the DLT observation period for the first 2 cycles of treatment.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=12 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=6 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)

Population: The full analysis set (FAS) will include all participants who receive at least one dose of study drug. Participants will be classified according to the study treatment actually received. If a participant receives more than one treatment the participant will be classified according to the first study treatment received.

OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	50.0 Percentage of Participants 95% Confidence Interval 11.8 • Interval 11.8 to 88.2	53.8 Percentage of Participants 95% Confidence Interval 25.1 • Interval 25.1 to 80.8	33.3 Percentage of Participants 95% Confidence Interval 4.3 • Interval 4.3 to 77.7	39.0 Percentage of Participants 95% Confidence Interval 24.2 • Interval 24.2 to 55.5

SECONDARY outcome

Timeframe: Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)

Population: The PK concentration analysis sets are subsets of the safety analysis set including participants who have at least one concentration measurement for avelumab which they were assigned to receive,based on the treatment group.Overall number of participants analyzed=participants evaluable for this outcome measure and only those contributing to data for this outcome measure.Number analyzed=participants evaluable and contributing at specified time point.

The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter. Pharmacokinetic concentration analysis set was subset of safety analysis set and included participants who had at least one concentration measurement for avelumab or other study drugs which they were assigned to receive. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=40 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Serum Concentration of Avelumab Cycle 1/Day 1- 1 hour	173.3 Micrograms per milliliter Geometric Coefficient of Variation 26	172.2 Micrograms per milliliter Geometric Coefficient of Variation 18	284.1 Micrograms per milliliter Geometric Coefficient of Variation 33	300.2 Micrograms per milliliter Geometric Coefficient of Variation 32
Serum Concentration of Avelumab Cycle 1/Day 15- 336 hours	12.32 Micrograms per milliliter Geometric Coefficient of Variation 47	9.570 Micrograms per milliliter Geometric Coefficient of Variation 92	16.51 Micrograms per milliliter Geometric Coefficient of Variation 68	14.71 Micrograms per milliliter Geometric Coefficient of Variation 74
Serum Concentration of Avelumab Cycle 2/Day 1- pre-dose	4.780 Micrograms per milliliter Geometric Coefficient of Variation 44	3.754 Micrograms per milliliter Geometric Coefficient of Variation 115	4.328 Micrograms per milliliter Geometric Coefficient of Variation 332	5.013 Micrograms per milliliter Geometric Coefficient of Variation 196
Serum Concentration of Avelumab Cycle 2/Day 1- 1 hour	164.2 Micrograms per milliliter Geometric Coefficient of Variation 33	197.0 Micrograms per milliliter Geometric Coefficient of Variation 18	104.5 Micrograms per milliliter Geometric Coefficient of Variation 1474	311.9 Micrograms per milliliter Geometric Coefficient of Variation 36
Serum Concentration of Avelumab Cycle 2/Day 15- 336 hours	16.87 Micrograms per milliliter Geometric Coefficient of Variation 24	13.55 Micrograms per milliliter Geometric Coefficient of Variation 33	16.82 Micrograms per milliliter Geometric Coefficient of Variation 137	18.66 Micrograms per milliliter Geometric Coefficient of Variation 75
Serum Concentration of Avelumab Cycle 3/Day 1- pre-dose	8.122 Micrograms per milliliter Geometric Coefficient of Variation 40	5.651 Micrograms per milliliter Geometric Coefficient of Variation 75	4.878 Micrograms per milliliter Geometric Coefficient of Variation 662	6.771 Micrograms per milliliter Geometric Coefficient of Variation 104
Serum Concentration of Avelumab Cycle 3/Day 1- 1 hour	147.0 Micrograms per milliliter Geometric Coefficient of Variation 35	204.0 Micrograms per milliliter Geometric Coefficient of Variation 28	93.81 Micrograms per milliliter Geometric Coefficient of Variation 2989	296.8 Micrograms per milliliter Geometric Coefficient of Variation 36
Serum Concentration of Avelumab Cycle 3/Day 15- 336 hours	19.40 Micrograms per milliliter Geometric Coefficient of Variation 14	17.15 Micrograms per milliliter Geometric Coefficient of Variation 40	26.17 Micrograms per milliliter Geometric Coefficient of Variation 74	22.55 Micrograms per milliliter Geometric Coefficient of Variation 79
Serum Concentration of Avelumab Cycle 6/Day 1- pre-dose	11.38 Micrograms per milliliter Geometric Coefficient of Variation 24	9.518 Micrograms per milliliter Geometric Coefficient of Variation 65	10.86 Micrograms per milliliter Geometric Coefficient of Variation 165	10.39 Micrograms per milliliter Geometric Coefficient of Variation 233
Serum Concentration of Avelumab Cycle 6/Day 1- 1 hour	92.53 Micrograms per milliliter Geometric Coefficient of Variation 203	208.3 Micrograms per milliliter Geometric Coefficient of Variation 23	245.4 Micrograms per milliliter Geometric Coefficient of Variation 6	344.0 Micrograms per milliliter Geometric Coefficient of Variation 27
Serum Concentration of Avelumab Cycle 10/Day 1- pre-dose	9.523 Micrograms per milliliter Geometric Coefficient of Variation 33	8.695 Micrograms per milliliter Geometric Coefficient of Variation 115	6.620 Micrograms per milliliter Geometric Coefficient of Variation NA Data was not estimable due to low number of participants analyzed.	18.55 Micrograms per milliliter Geometric Coefficient of Variation 58
Serum Concentration of Avelumab Cycle 10/Day 1- 1 hour	179.0 Micrograms per milliliter Geometric Coefficient of Variation 38	222.0 Micrograms per milliliter Geometric Coefficient of Variation 27	6.040 Micrograms per milliliter Geometric Coefficient of Variation NA Data was not estimable due to low number of participants analyzed.	242.9 Micrograms per milliliter Geometric Coefficient of Variation 121
Serum Concentration of Avelumab Cycle 14/Day 1- pre-dose	14.97 Micrograms per milliliter Geometric Coefficient of Variation 28	13.37 Micrograms per milliliter Geometric Coefficient of Variation 77	12.24 Micrograms per milliliter Geometric Coefficient of Variation 523	16.49 Micrograms per milliliter Geometric Coefficient of Variation 57
Serum Concentration of Avelumab Cycle 14/Day 1- 1 hour	215.3 Micrograms per milliliter Geometric Coefficient of Variation 20	216.6 Micrograms per milliliter Geometric Coefficient of Variation 22	29.05 Micrograms per milliliter Geometric Coefficient of Variation 20555	402.2 Micrograms per milliliter Geometric Coefficient of Variation 19

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1

Population: The tumor tissue-based biomarker analysis set was subset of the safety analysis set and included participants who had at least one baseline and one on-treatment biomarker assessment for the same biomarker. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=4 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=5 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=39 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue	4.3 Mutations per megabase Standard Deviation 6.75 • Interval 6.75 to	2.8 Mutations per megabase Standard Deviation 2.76 • Interval 2.76 to	4.4 Mutations per megabase Standard Deviation 5.15 • Interval 5.15 to	2.5 Mutations per megabase Standard Deviation 2.88 • Interval 2.88 to

SECONDARY outcome

Timeframe: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

Population: Safety analysis set included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

Adverse event (AE) was any untoward medical occurrence in a participants who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs TEAEs	6 Participants	13 Participants	6 Participants	40 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Serious TEAEs	3 Participants	9 Participants	5 Participants	20 Participants

SECONDARY outcome

Timeframe: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

A treatment related AE included AEs related to at least one study drug in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study drug was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Treatment Related TEAEs	6 Participants	12 Participants	6 Participants	40 Participants

SECONDARY outcome

Timeframe: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using NCI CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher TEAEs were reported.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03	5 Participants	12 Participants	6 Participants	37 Participants

SECONDARY outcome

Timeframe: From screening up to 90 days after last dose of study drug (maximum up to 5 years approximately)

Participants with laboratory abnormalities of any Grade as per NCI CTCAE toxicity grading v4.03 were summarized:hematology(anemia,hemoglobin increased,lymphocyte count decreased,lymphocyte count increased, neutrophil count decreased,platelet count decreased and white blood cell decreased)and clinical chemistry(alanine aminotransferase increased,alkaline phosphatase,increased,aspartate,aminotransferase increased,blood bilirubin increased,cholesterol high,creatinine phosphokinase\[cpk\] increased,creatinine increased,gamma-glutamyl transferase\[ggt\] increased,hypercalcemia,hyperglycemia,hyperkalemia, hypermagnesemia,hypernatremia,hypertriglyceridemia,hypoalbuminemia,hypocalcemia,hypoglycemia,hypokalemia,hypomagnesemia,hyponatremia, hypophosphatemia,serum amylase increased and lipase increased).As per NCI CTCAE toxicity grading v4.03, Grade1=mild;Grade2=moderate;Grade3=severe;Grade4=life-threatening;Grade 5=death.Parameters with at least 1 participant with abnormal value are reported.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=40 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade ALANINE AMINOTRANSFERASE INCREASED	1 Participants	1 Participants	0 Participants	3 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade ALKALINE PHOSPHATASE INCREASED	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade ASPARTATE AMINOTRANSFERASE INCREASED	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade BLOOD BILIRUBIN INCREASED	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade CPK INCREASED	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade CREATININE INCREASED	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade GGT INCREASED	0 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERGLYCEMIA	2 Participants	2 Participants	0 Participants	4 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERKALEMIA	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPOKALEMIA	1 Participants	0 Participants	0 Participants	5 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPONATREMIA	0 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade LIPASE INCREASED	1 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade SERUM AMYLASE INCREASED	0 Participants	2 Participants	0 Participants	4 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPOPHOSPHATEMIA	2 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPOMAGNESEMIA	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPOCALCEMIA	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERTRIGLYCERIDEMIA	0 Participants	3 Participants	0 Participants	2 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERNATREMIA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERMAGNESEMIA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade HYPERCALCEMIA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade ANEMIA	2 Participants	5 Participants	0 Participants	6 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade LYMPHOCYTE COUNT DECREASED	3 Participants	5 Participants	1 Participants	7 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade LYMPHOCYTE COUNT INCREASED	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade NEUTROPHIL COUNT DECREASED	3 Participants	8 Participants	3 Participants	21 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade PLATELET COUNT DECREASED	3 Participants	2 Participants	0 Participants	11 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade WHITE BLOOD CELL DECREASED	2 Participants	7 Participants	3 Participants	16 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to last dose of study drug (maximum up to 5 years approximately)

Population: The immunogenicity analysis set is a subset of the safety analysis set and will include participants who have at least one ADA/nAb sample collected for avelumab.

Blood samples were collected for assessment of avelumab ADAs using a tiered assay and confirmed positive samples were tested for neutralizing antibodies (nAb).

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab ADA ever positive	0 Participants	5 Participants	1 Participants	9 Participants
Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab NAB ever positive	NA Participants The data for NAB was not generated due to low observed immunogenicity.	NA Participants The data for NAB was not generated due to low observed immunogenicity.	NA Participants The data for NAB was not generated due to low observed immunogenicity.	NA Participants The data for NAB was not generated due to low observed immunogenicity.

SECONDARY outcome

Timeframe: From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5 years approximately)

Population: The full analysis set (FAS) included all participants who received at least 1 dose of study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. The median duration of PFS was not derived for less than (\<) 10 participants.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment	NA Months Median and 95% CI were not estimated for \<10 participants.	9.8 Months Interval 2.2 to Upper limit of 95% CI was not reached due to fewer number of participants with event.	NA Months Median and 95% CI were not estimated for \<10 participants.	5.4 Months Interval 2.9 to 6.0

SECONDARY outcome

Timeframe: From first dose of study treatment until death due to any cause (maximum up to 5 years approximately)

OS was defined as the time from the first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. The median duration of OS was not derived for less than (\<) 10 participants.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Overall Survival (OS)	NA Months Median and 95% CI were not estimated for \<10 participants.	18.1 Months Interval 5.0 to Upper limit of 95% CI was not reached due to fewer number of participants with event.	NA Months Median and 95% CI were not estimated for \<10 participants.	15.1 Months Interval 8.7 to 22.0

SECONDARY outcome

Timeframe: From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 5 years approximately)

DOR was defined as time from first documentation of objective response (confirmed CR or PR) to the date of first PD documentation or death due to any cause, whichever occurs first. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. Median DOR was not derived for \< 5 participants.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=3 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=7 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=2 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=16 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment	NA Months Median and 95% CI were not estimated for \<5 participants.	9.6 Months Interval 4.0 to Upper limit of 95% CI was not reached due to fewer number of participants with event.	NA Months Median and 95% CI were not estimated for \<5 participants.	NA Months Interval 4.2 to Median and Upper limit of 95% CI were not reached due to fewer number of participants with event.

SECONDARY outcome

Timeframe: From first dose of study treatment until first documentation of CR or PR (maximum up to 5 years approximately)

TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=3 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=7 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=2 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=16 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment	2.8 Months Full Range 1.3 • Interval 1.3 to 4.1	1.4 Months Full Range 1.1 • Interval 1.1 to 1.5	1.3 Months Full Range 1.3 • Interval 1.3 to 1.3	1.5 Months Full Range 1.3 • Interval 1.3 to 4.3

SECONDARY outcome

Timeframe: Baseline and Cycle 2 Day 8 (each cycle of 21 days)

Population: FAS included all participants who received at least one dose of study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

PD-L1 expression was determined using the Ventana PD-L1 SP263 IHC assay. PD-L1-positive status in UC cohorts was defined using an algorithm that combines assessments of PD-L1 staining on tumor and immune cells scored by pathologists and in NSCLC cohorts was defined as PD-L1 expression on \>=1% of tumor cells. PD-L1 expression at baseline and on-treatment were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m\^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose \[mg\] = target AUC \* glomerular filtration rate\[GFR\] milliliter per minute \[mL/min\] + 25, and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin n=13 Participants Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin n=6 Participants Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m\^2 and carboplatin dose at AUC 5 (carboplatin dose \[mg\] = target AUC \* GFR mL/min + 25), and maximum carboplatin dose = target AUC \[mg\min/mL\] \ 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first.	Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin n=41 Participants Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m\^2 and gemcitabine 1000 mg/m\^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm.
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression Baseline- Positive PD-L1	0 Participants	6 Participants	1 Participants	28 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression Baseline- Negative PD-L1	4 Participants	7 Participants	4 Participants	13 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression Baseline- Unknown PD-L1	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression On-treatment (Cycle 2 Day 8)- Positive PD-L1	0 Participants	2 Participants	1 Participants	3 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression On-treatment (Cycle 2 Day 8)- Negative PD-L1	2 Participants	1 Participants	0 Participants	6 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression On-treatment (Cycle 2 Day 8)- Unknown PD-L1	4 Participants	10 Participants	5 Participants	32 Participants

Adverse Events

Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin

Serious events: 3 serious events

Other events: 6 other events

Deaths: 3 deaths

Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin

Serious events: 9 serious events

Other events: 13 other events

Deaths: 8 deaths

Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin

Serious events: 5 serious events

Other events: 6 other events

Deaths: 5 deaths

Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin

Serious events: 20 serious events

Other events: 40 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 8007181021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER